Submitted on December 27, 2006
Accepted on February 27, 2007
The Intestinotrophic Effects of Exogenous Insulin-Like Growth Factor-I (IGF-I) Are Not Diminished in IGF Binding Protein-5 Knock-Out Mice
Sangita G Murali1, Xiaowen Liu1, David Warren Nelson1, Angela K Hull1, Michael Grahn1, Murray K Clayton2, John E Pintar3, and Denise M. Ney4*
1 Nutritional Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
2 Statistics and Plant Pathology, University of Wisconsin-Madison, Madison, Wisconsin, United States
3 Neurosciences and Cell Biology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey, United States
4 Department of Nutritional Sciences, University of Wisconsin-Madison, Madison,, Wisconsin, United States
* To whom correspondence should be addressed. E-mail: ney{at}nutrisci.wisc.edu.
Insulin-like growth factor binding protein-5 (IGFBP-5) modulates the availability of insulin-like growth factor-I (IGF-I) to its receptor and potentiates the intestinotrophic action of IGF-I. Our aim was to test the hypothesis that stimulation of intestinal growth due to coinfusion of IGF-I with total parenteral nutrition (TPN) solution is dependent on increased expression of IGFBP-5 by conducting studies in IGFBP-5 knock out (KO) mice. IGFBP-5 KO, heterozygote (HT) and wild type (WT) male and female mice were maintained with TPN or TPN plus coinfusion of IGF-I (rhIGF-I; 2.5 mg/kg/d) for 5 d. The concentration of IGF-I in serum was 73% greater (p<0.0001) in mice given TPN + IGF-I infusion compared to TPN alone. IGF-I attenuated the 2-3 g loss of body weight associated with TPN in WT mice, whereas KO and HT mice did not show improvement in body weight with IGF-I treatment. KO and HT mice had significantly greater levels of circulating IGFBPs compared to WT mice. Intestinal growth due to IGF-I was observed in all groups treated with IGF-I based on greater concentrations of protein and DNA in small intestine and colon and significantly greater crypt depth and muscularis thickness in jejunum. Jejunal expression of IGFBP-5 mRNA was greater in WT mice whereas IGF-I binding protein-3 (IGFBP-3) mRNA was greater in KO mice treated with IGF-I. In summary, the absence of the IGFBP-5 gene did not block the ability of IGF-I to stimulate intestinal growth possibly because greater jejunal expression of IGFBP-3 compensates for the absence of IGFBP-5.
